PDF(Pubmed)
Abstract：
Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after one to three vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes.
A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from four countries. Standardised immune assays were performed pre and post three vaccine doses (V1-3).
In the total cohort, there were incremental increases in antibody titres after each vaccine dose (p <0.0001). Factors associated with reduced antibody responses were age and LT, whereas heterologous vaccination, prior COVID-19 and mRNA platforms were associated with greater responses. Although antibody titres decreased between post-V2 and pre-V3 (p = 0.012), patients with AIH, VLD, and cirrhosis had equivalent antibody responses to HCs post-V3. LTRs had lower and more heterogenous antibody titres than other groups, including post-V3 where 9% had no detectable antibodies; this was heavily influenced by intensity of immunosuppression. Vaccination increased T-cell IFNγ responses in all groups except LTRs. Patients with liver disease had lower functional antibody responses against nine Omicron subvariants and reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type. 122 cases of breakthrough COVID-19 were reported of which 5/122 (4%) were severe. Of the severe cases, 4/5 (80%) occurred in LTRs and 2/5 (40%) had no serological response post-V2.
After three COVID-19 vaccines, patients with liver disease generally develop robust antibody and T-cell responses to vaccination and have mild COVID-19. However, LTRs have sustained no/low antibody titres and appear most vulnerable to severe disease.
Standardised assessments of the immune response to different COVID-19 vaccines in patients with liver disease are lacking. We performed antibody and T-cell assays at multiple timepoints following up to three vaccine doses in a large cohort of patients with a range of liver conditions. Overall, the three most widely available vaccine platforms were immunogenic and appeared to protect against severe breakthrough COVID-19. This will provide reassurance to patients with chronic liver disease who were deemed at high risk of severe COVID-19 during the pre-vaccination era, however, liver transplant recipients had the lowest antibody titres and remained vulnerable to severe breakthrough infection. We also characterise the immune response to multiple SARS-CoV-2 variants and describe the interaction between disease type, severity, and vaccine platform. These insights may prove useful in the event of future viral infections which also require rapid vaccine development and delivery to patients with liver disease.
A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from four countries. Standardised immune assays were performed pre and post three vaccine doses (V1-3).
In the total cohort, there were incremental increases in antibody titres after each vaccine dose (p <0.0001). Factors associated with reduced antibody responses were age and LT, whereas heterologous vaccination, prior COVID-19 and mRNA platforms were associated with greater responses. Although antibody titres decreased between post-V2 and pre-V3 (p = 0.012), patients with AIH, VLD, and cirrhosis had equivalent antibody responses to HCs post-V3. LTRs had lower and more heterogenous antibody titres than other groups, including post-V3 where 9% had no detectable antibodies; this was heavily influenced by intensity of immunosuppression. Vaccination increased T-cell IFNγ responses in all groups except LTRs. Patients with liver disease had lower functional antibody responses against nine Omicron subvariants and reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type. 122 cases of breakthrough COVID-19 were reported of which 5/122 (4%) were severe. Of the severe cases, 4/5 (80%) occurred in LTRs and 2/5 (40%) had no serological response post-V2.
After three COVID-19 vaccines, patients with liver disease generally develop robust antibody and T-cell responses to vaccination and have mild COVID-19. However, LTRs have sustained no/low antibody titres and appear most vulnerable to severe disease.
Standardised assessments of the immune response to different COVID-19 vaccines in patients with liver disease are lacking. We performed antibody and T-cell assays at multiple timepoints following up to three vaccine doses in a large cohort of patients with a range of liver conditions. Overall, the three most widely available vaccine platforms were immunogenic and appeared to protect against severe breakthrough COVID-19. This will provide reassurance to patients with chronic liver disease who were deemed at high risk of severe COVID-19 during the pre-vaccination era, however, liver transplant recipients had the lowest antibody titres and remained vulnerable to severe breakthrough infection. We also characterise the immune response to multiple SARS-CoV-2 variants and describe the interaction between disease type, severity, and vaccine platform. These insights may prove useful in the event of future viral infections which also require rapid vaccine development and delivery to patients with liver disease.
摘要：
目的：在不同肝病患者中缺乏不同COVID-19疫苗的免疫原性比较评估。SARS-CoV-2特异性T细胞和抗体反应在一到三种疫苗后与COVID-19临床结果进行纵向评估。
方法：849名肝硬化患者，自身免疫性肝炎（AIH），血管性肝病（VLD），我们从4个国家招募了肝移植受者(LTR)和健康对照者(HC).在三种疫苗(V1-3)之前和之后进行标准化的免疫测定。
结果：在总队列中，每次接种疫苗后抗体滴度均有递增增加(p<0.0001).与抗体反应降低相关的因素是年龄和LT，而异源疫苗接种，先前的COVID-19和mRNA平台与更大的反应相关。尽管在V2后和V3前之间抗体滴度降低（p=0.012），AIH患者,VLD,和肝硬化有相同的抗体应答HC后V3。LTR比其他组具有更低和更高的异质性抗体滴度，包括V3后，其中9％的患者没有检测到抗体；这在很大程度上受到免疫抑制强度的影响。除LTR外，所有组的疫苗接种均增加了T细胞IFNγ反应。与野生型相比，肝病患者对9种Omicron亚变体的功能抗体反应较低，对OmicronBA.1特异性肽的T细胞反应降低。报告122例突破性COVID-19，其中5/122（4%）为重症。在严重的病例中，4/5（80％）发生在LTR中，2/5（40％）在V2后没有血清学反应。
结论：在三种COVID-19疫苗接种后，肝病患者通常会对疫苗接种产生强烈的抗体和T细胞反应，并且患有轻度COVID-19。然而,LTR具有持续的无/低抗体滴度,并且似乎最容易受到严重疾病的影响。
缺乏对肝病患者对不同COVID-19疫苗的免疫反应的标准化评估。我们在多个时间点进行了抗体和T细胞测定，在大量具有一系列肝脏疾病的患者的三个疫苗剂量之后。总的来说,三种最广泛使用的疫苗平台具有免疫原性,似乎可以预防严重的突破性COVID-19.这将为在疫苗接种前被认为有严重COVID-19高风险的慢性肝病患者提供保证，然而,肝移植受者的抗体滴度最低，并且仍然容易受到严重的突破性感染。我们还描述了对多种SARS-CoV-2变体的免疫反应，并描述了疾病类型之间的相互作用。严重程度,疫苗平台。这些见解可能在未来的病毒感染事件中被证明是有用的，这也需要快速的疫苗开发和递送到肝脏患者。
方法：849名肝硬化患者，自身免疫性肝炎（AIH），血管性肝病（VLD），我们从4个国家招募了肝移植受者(LTR)和健康对照者(HC).在三种疫苗(V1-3)之前和之后进行标准化的免疫测定。
结果：在总队列中，每次接种疫苗后抗体滴度均有递增增加(p<0.0001).与抗体反应降低相关的因素是年龄和LT，而异源疫苗接种，先前的COVID-19和mRNA平台与更大的反应相关。尽管在V2后和V3前之间抗体滴度降低（p=0.012），AIH患者,VLD,和肝硬化有相同的抗体应答HC后V3。LTR比其他组具有更低和更高的异质性抗体滴度，包括V3后，其中9％的患者没有检测到抗体；这在很大程度上受到免疫抑制强度的影响。除LTR外，所有组的疫苗接种均增加了T细胞IFNγ反应。与野生型相比，肝病患者对9种Omicron亚变体的功能抗体反应较低，对OmicronBA.1特异性肽的T细胞反应降低。报告122例突破性COVID-19，其中5/122（4%）为重症。在严重的病例中，4/5（80％）发生在LTR中，2/5（40％）在V2后没有血清学反应。
结论：在三种COVID-19疫苗接种后，肝病患者通常会对疫苗接种产生强烈的抗体和T细胞反应，并且患有轻度COVID-19。然而,LTR具有持续的无/低抗体滴度,并且似乎最容易受到严重疾病的影响。
缺乏对肝病患者对不同COVID-19疫苗的免疫反应的标准化评估。我们在多个时间点进行了抗体和T细胞测定，在大量具有一系列肝脏疾病的患者的三个疫苗剂量之后。总的来说,三种最广泛使用的疫苗平台具有免疫原性,似乎可以预防严重的突破性COVID-19.这将为在疫苗接种前被认为有严重COVID-19高风险的慢性肝病患者提供保证，然而,肝移植受者的抗体滴度最低，并且仍然容易受到严重的突破性感染。我们还描述了对多种SARS-CoV-2变体的免疫反应，并描述了疾病类型之间的相互作用。严重程度,疫苗平台。这些见解可能在未来的病毒感染事件中被证明是有用的，这也需要快速的疫苗开发和递送到肝脏患者。
